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HLA Screening in Reducing the Risk of Antiepileptic Drug-induced Cutaneous Adverse Reactions

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03184597
Recruitment Status : Recruiting
First Posted : June 12, 2017
Last Update Posted : September 5, 2018
Sponsor:
Collaborators:
Guangzhou First People's Hospital
West China Hospital
Guangdong Provincial People's Hospital
First Affiliated Hospital of Jinan University
Guangdong 999 Brain Hospital
First Affiliated Hospital, Sun Yat-Sen University
Wuhan Women and Children's Medical Center
First People's Hospital, Shunde China
Information provided by (Responsible Party):
Second Affiliated Hospital of Guangzhou Medical University

Tracking Information
First Submitted Date  ICMJE June 9, 2017
First Posted Date  ICMJE June 12, 2017
Last Update Posted Date September 5, 2018
Actual Study Start Date  ICMJE August 1, 2017
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2017)
AEDs-induced cADRs incidence [ Time Frame: 3 months ]
the incidence of AEDs-induced cADRs within the first 3 months of commencing an aromatic AED
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03184597 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE HLA Screening in Reducing the Risk of Antiepileptic Drug-induced Cutaneous Adverse Reactions
Official Title  ICMJE HLA Screening in Reducing the Risk of Antiepileptic Drug-induced Cutaneous Adverse Reactions: a Multicenter Clinical Study
Brief Summary

Cutaneous adverse drug reactions (cADRs) include mild maculopapular exanthema (MPE) and severe cutaneous reactions such as hypersensitivity syndrome, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). cADRs are considered as a major public health issue because of their potentially life-threatening morbidity, especially severe cutaneous reactions. The incidence of SJS/TEN is estimated to vary from 1 in 1,000 to 10,000 drug exposures, and its mortality is as high as 35%. Antiepileptic drugs (AEDs), particularly those with aromatic ring structures such as carbamazepine (CBZ), oxcarbazepine (OXC), lamotrigine (LTG), phenobarbital (PB), and phenytoin (PHT), are among the most common causes of severe cutaneous reactions. The incidence of AED-induced SJS was estimated as 0.2% and all cases occurred in individuals receiving aromatic AEDs.

Previous studies have validated that the human leukocyte antigen (HLA) allele HLA-B*15:02 is strongly associated with CBZ-induced SJS/TEN in southern Han Chinese and populations in southeast Asia. Our recent studies indicated that HLA-A*24:02 is a common genetic risk factor for CBZ-, LTG-, and PHT-induced SJS/TEN. It is also associated with MPE. Additionally, another four alleles, including HLA-B*15:01, HLA-B*15:11, HLA-A*02:01,and HLA-DRB1*01:01, were showed to be potential risk factors for aromatic AEDs-induced SJS/TEN. In 2007, the US Food and Drug Administration issued the safety alert that recommended HLA-B*15:02 screening for people with Asian ancestry before starting CBZ, and avoidance of the drug if the test is positive. Subsequent studies from Taiwan, Hong Kong and Thailand demonstrated that HLA-B*15:02 screening before commencing CBZ can significantly reduce the incidence of CBZ-induced SJS/TEN. However, the overall incidence of AEDs-induced SJS/TEN remained unchanged in Hong Kong, as PHT-induced SJS/TEN increased when CBZ-SJS/TEN decreased. Moreover, no study focuses on the incidences of AEDs-induced cADRs with and without HLA screening before commencing aromatic AEDs. Therefore, we are planning to conduct a multicenter prospective study to examine the reduction of AEDs-induced cADRs after the HLA screening prior to the beginning of aromatic AEDs administration.

Detailed Description In this prospective study, 4000 or more patients from multicenters in southern China will be recruited. A HLA screening will be conducted before these patients start aromatic AEDs treatments. According to the HLA genotype, these patients will be divided into four groups that are three positive groups with different risk alleles and one negative group with no known risk allele. Aromatic AEDs were avoided or administrated with caution according to the risk level in the three positive groups, while they can be prescribed in the negative group. The effectiveness of HLA screening prior to the beginning of aromatic AEDs administration will be observed by the reduction of overall incidence of AEDs-induced cADRs.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Epilepsy
  • Neuropathy
  • Psychiatric Illness
  • Blepharospasm
Intervention  ICMJE Diagnostic Test: HLA screening before commencing aromatic AEDs
When the risk HLA alleles are tested positive for the patients, aromatic AEDs were avoided or administrated with caution according to the risk level.
Study Arms  ICMJE
  • Experimental: Group with two strong risk factors
    When HLA screening before commencing aromatic AEDs shows positive for both HLA-A*24:02 and HLA-B*15:02 in a patient, aromatic AEDs were not administrated for this patient.
    Intervention: Diagnostic Test: HLA screening before commencing aromatic AEDs
  • Experimental: Group with one strong risk factors

    When HLA screening before commencing aromatic AEDs shows positive for HLA-B*15:02, carbamazepine (CBZ) was not administrated, and other aromatic AEDs were prescribed with caution or avoided if alternative non-aromatic AEDs can be prescribed instead.

    When HLA screening before commencing aromatic AEDs shows positive for HLA-B*15:01 or HLA-A*24:02, aromatic AEDs were prescribed with caution or avoided if alternative non-aromatic AEDs can be prescribed instead.

    Intervention: Diagnostic Test: HLA screening before commencing aromatic AEDs
  • Experimental: Group with one potential risk factors
    When HLA screening before commencing aromatic AEDs shows positive for any potential risk allele such as HLA-B*15:11, HLA-A*02:01and HLA-DRB1*01:01, aromatic AEDs were prescribed with caution or avoided if alternative non-aromatic AEDs can be prescribed instead.
    Intervention: Diagnostic Test: HLA screening before commencing aromatic AEDs
  • Experimental: Group without known risk factors
    When HLA screening before commencing aromatic AEDs shows negative for any known HLA risk allele , aromatic AEDs was administrated to these patients.
    Intervention: Diagnostic Test: HLA screening before commencing aromatic AEDs
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 9, 2017)
4000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients who are going to receive a kind of aromatic AEDs including CBZ, OXC, LTG, PHT, and PB as a new therapy. An AED was deemed newly commenced if there was no record of its prescription in at least the previous 12 months.
  2. Ethnic Han Chinese. None of the biological grandparents of the participants were from other races.

Exclusion Criteria:

  1. individuals who are not of Han Chinese descent.
  2. individuals who had undergone bone marrow transplantation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Wei-Ping Liao, M.D.,Ph.D. +86-20-34152625 wpliao@163.net
Contact: Na He, Ph.D. +86-20-34152640 henachilli@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03184597
Other Study ID Numbers  ICMJE 2017-hs-30
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The clinical data and HLA genotype of the participant will be shared in the collaborators
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: 2017 July - 2021 July
Responsible Party Second Affiliated Hospital of Guangzhou Medical University
Study Sponsor  ICMJE Second Affiliated Hospital of Guangzhou Medical University
Collaborators  ICMJE
  • Guangzhou First People's Hospital
  • West China Hospital
  • Guangdong Provincial People's Hospital
  • First Affiliated Hospital of Jinan University
  • Guangdong 999 Brain Hospital
  • First Affiliated Hospital, Sun Yat-Sen University
  • Wuhan Women and Children's Medical Center
  • First People's Hospital, Shunde China
Investigators  ICMJE
Principal Investigator: Wei-Ping Liao, M.D.,Ph.D. Second Affiliated Hospital of Guangzhou Medical University
PRS Account Second Affiliated Hospital of Guangzhou Medical University
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP